title: Actin depolymerization factor/cofilin activation regulates actin polymerization and tension development in canine tracheal smooth muscle.
abstract: The contractile activation of airway smooth muscle tissues stimulates actin polymerization, and the inhibition of actin polymerization inhibits tension development. Actin-depolymerizing factor (ADF) and cofilin are members of a family of actin-binding proteins that mediate the severing of F-actin when activated by dephosphorylation at serine 3. The role of ADF/cofilin activation in the regulation of actin dynamics and tension development during the contractile activation of smooth muscle was evaluated in intact canine tracheal smooth muscle tissues. Two-dimensional gel electrophoresis revealed that ADF and cofilin exist in similar proportions in the muscle tissues, and that approximately 40% of the total ADF/cofilin in unstimulated tissues is phosphorylated. Phospho-ADF/cofilin decreased concurrently with tension development in response to stimulation with acetylcholine (ACh) or potassium depolarization indicating the activation of ADF/cofilin. Expression of an inactive phospho-cofilin mimetic (cofilin S3E) but not wild type cofilin in the smooth muscle tissues inhibited endogenous ADF/cofilin dephosphorylation and ACh-induced actin polymerization. Expression of cofilin S3E in the tissues depressed tension development in response to ACh, but it did not affect myosin light chain phosphorylation. The ACh-induced dephosphorylation of ADF/cofilin required the Ca2+-dependent activation of calcineurin (PP2B). The results indicate that the activation of ADF/cofilin is regulated by contractile stimulation in tracheal smooth muscle and that cofilin activation is required for actin polymerization and tension development in response to contractile stimulation.
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhao
authors.forename: Liping
authors.initials: L
authors.lastname: Du
authors.forename: Youliang
authors.initials: Y
authors.lastname: Huang
authors.forename: Yidi
authors.initials: Y
authors.lastname: Wu
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Gunst
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000199:Actins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000378:metabolism; D051338:Cofilin 1 / Q000378:metabolism*; D004285:Dogs; D015180:Electrophoresis, Gel, Two-Dimensional; D005786:Gene Expression Regulation; D008954:Models, Biological; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D014132:Trachea / Q000378:metabolism*
chemical_list: D000199:Actins; D065095:Calcineurin Inhibitors; D051338:Cofilin 1; D000109:Acetylcholine; D002118:Calcium